The Effect of Different Intraperitoneal Hyperthermic Chemotherapy (HIPEC) Regimens on Serum Electrolyte Levels: A Comparison of Oxaliplatin and Mitomycin C
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Patient Selection
2.2. Treatment Allocation and Surgical Technique
2.3. HIPEC Regimens
2.4. Laboratory Analysis and Sampling
2.5. Perioperative Standardization
2.6. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Kuijpers, A.M.; Mirck, B.; Aalbers, A.G.; Nienhuijs, S.W.; de Hingh, I.H.; Wiezer, M.J.; van Ramshorst, B.; van Ginkel, R.J.; Havenga, K.; Bremers, A.J.; et al. Cytoreduction and HIPEC in The Netherlands: Nationwide long-term outcome following the Dutch protocol. Ann. Surg. Oncol. 2013, 20, 4224–4230. [Google Scholar] [CrossRef] [PubMed]
- Quénet, F.; Elias, D.; Roca, L.; Goéré, D.; Ghouti, L.; Pocard, M.; Facy, O.; Arvieux, C.; Lorimier, G.; Pezet, D.; et al. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021, 22, 256–266. [Google Scholar] [CrossRef] [PubMed]
- Pahlkotter, M.; Digney, B.W.; Yu, A.T.; Schmidt, L.; Cohen, N.A.; Sarpel, U.; Lambert, L. The history of cytoreduction and HIPEC: Heating up or just blowing smoke? J. Surg. Oncol. 2024, 130, 1130–1138. [Google Scholar] [CrossRef] [PubMed]
- Bhatt, A.; de Hingh, I.; Van Der Speeten, K.; Hubner, M.; Deraco, M.; Bakrin, N.; Villeneuve, L.; Kusamura, S.; Glehen, O. HIPEC Methodology and Regimens: The Need for an Expert Consensus. Ann. Surg. Oncol. 2021, 28, 9098–9113. [Google Scholar] [CrossRef] [PubMed]
- Kusamura, S.; Bhatt, A.; van Der Speeten, K.; Kepenekian, V.; Hübner, M.; Eveno, C.; de Hingh, I.; Delhorme, J.B.; Taibi, A.; Villeneuve, L.; et al. Review of 2022 PSOGI/RENAPE Consensus on HIPEC. J. Surg. Oncol. 2024, 130, 1290–1298. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Somashekhar, S.P.; Surendran, A.K.; Goyal, D.; Rawat, S.; Aggarwal, S.; Selvasekar, C.; Parikh, P.M. Current Status of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Colorectal Cancer (CRC). South Asian J. Cancer 2025, 13, 267–273. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Kusamura, S.; Baratti, D.; Younan, R.; Deraco, M. The Delphi approach to Attain consensus in methodology of local regional therapy for peritoneal surface malignancy. J. Surg. Oncol. 2008, 98, 217–219. [Google Scholar] [CrossRef] [PubMed]
- Fisher, O.M.; Brown, C.; Esquivel, J.; Larsen, S.G.; Liauw, W.; Alzahrani, N.A.; Morris, D.L.; Kepenekian, V.; Sourrouille, I.; Dumont, F.; et al. Hyperthermic intraperitoneal chemotherapy in colorectal cancer. BJS Open 2024, 8, zrae017. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Gough, S.M.; Thevelein, B.; Brainard, B.M.; Koenig, A. The sodium correction factor for dogs undergoing treatment for a hyperglycemic crisis is a 1.6-mEq/L decrease in sodium per 100-mg/dL increase in glucose. J. Am. Vet. Med. Assoc. 2024, 262, 1069–1075. [Google Scholar] [CrossRef] [PubMed]
- Alexander, H.R. Invited Commentary: Ten-Year Outcome of a Randomized Trial: Cytoreduction and HIPEC with Mitomycin C Versus Oxaliplatin for Appendiceal Neoplasm with Peritoneal Dissemination, by Levine et al. Ann. Surg. Oncol. 2025, 32, 1420–1421. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Wu, Q.; Wei, M.; Deng, X.; Gu, C.; Wang, Z. Oxaliplatin versus mitomycin C in HIPEC for peritoneal metastasis from colorectal cancer: A systematic review and meta-analysis of comparative studies. Int. J. Color. Dis. 2020, 35, 1831–1839. [Google Scholar] [CrossRef] [PubMed]
- Rueth, N.M.; Murray, S.E.; Huddleston, S.J.; Abbott, A.M.; Greeno, E.W.; Kirstein, M.N.; Tuttle, T.M. Severe electrolyte disturbances after hyperthermic intraperitoneal chemotherapy: Oxaliplatin versus mitomycin C. Ann. Surg. Oncol. 2011, 18, 174–180. [Google Scholar] [CrossRef] [PubMed]
- Spiliotis, J.; Kalles, V.; Prodromidou, A.; Raptis, A.; Ferfelis, M.; Christopoulou, A.; Tsiatas, M. Mitomycin-C versus oxaliplatin during cytoreductive surgery and HIPEC for peritoneal metastases secondary to colorectal carcinoma: A retrospective analysis. J. BUON 2021, 26, 1260–1265. [Google Scholar] [PubMed]
- Cheng, F.; Zhang, R.; Sun, C.; Ran, Q.; Zhang, C.; Shen, C.; Yao, Z.; Wang, M.; Song, L.; Peng, C. Oxaliplatin-induced peripheral neurotoxicity in colorectal cancer patients: Mechanisms, pharmacokinetics and strategies. Front. Pharmacol. 2023, 14, 1231401. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Mauri, G.; Gori, V.; Bonazzina, E.; Amatu, A.; Tosi, F.; Bencardino, K.; Ruggieri, L.; Patelli, G.; Arena, S.; Bardelli, A.; et al. Oxaliplatin retreatment in metastatic colorectal cancer: Systematic review and future research opportunities. Cancer Treat. Rev. 2020, 91, 102112. [Google Scholar] [CrossRef] [PubMed]
- Ye, J.W.; Hu, H.B.; Luo, R.; Wang, H.M.; Huang, R.K.; Chu, L.L.; Wang, H. Intraperitoneal chemotherapy for colorectal cancer peritoneal metastasis. Zhonghua Wei Chang Wai Ke Za Zhi 2024, 27, 646–652. (In Chinese) [Google Scholar] [CrossRef] [PubMed]
- Raytis, J.L.; Lew, M.W. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Intraoperative Electrolyte Disturbances—Implications for Anesthetic Management. Open J. Anesthesiol. 2014, 4, 240–243. [Google Scholar] [CrossRef]
- Shrimanker, I.; Bhattarai, S. Electrolytes. In StatPearls [Internet]; StatPearls Publishing: Treasure Island, FL, USA, 2025. [Google Scholar] [PubMed]
- Drigotas, C.; Loftus, A.W.; Ammori, J.B.; Rothermel, L.D.; Hoehn, R.S. Perfusion Strategies for Cytoreductive Surgery With Heated Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma. J. Surg. Oncol. 2025, 131, 310–315. [Google Scholar] [CrossRef] [PubMed]
Oxaliplatin (n = 16) | Mitomycin C (n = 19) | p Value | |
---|---|---|---|
Age (years) | 0.520 | ||
Mean | 54.2 | 53.8 | |
Median | 56.5 | 58 | |
Range | 24–70 | 25–70 | |
Gender [n, (%)] | 0.235 | ||
Male | 32 (51.6%) | 8 (40%) | |
Female | 30 (48.4%) | 12 (60%) | |
Primary disease [n (%)] | 0.06 | ||
Colorectal cancer | 46 (74.2%) | 11 (55%) | |
Psödomiksoma peritonei | 16 (25.8%) | 9 (45%) | |
Intensive care unit stay (days) | 0.392 | ||
Mean | 1.2 | 1.4 | |
Median (range) | 1 (1–5) | 1 (1–5) |
Electrolytea | Pre-HIPEC Average | Post-HIPEC Average | p-Value | Clinically Significant |
---|---|---|---|---|
Sodium (mmol/L) | 139.5 | 136.4 | 0.936 | Within normal range |
Potassium (mmol/L) | 3.5 | 3.5 | 0.755 | Stable |
Bicarbonate (mmol/L) | 20.7 | 21.8 | 0.219 | Slight improvement |
Glucose (mmol/L) | 182.7 | 180.1 | 0.168 | Remained stable |
Lactate (mmol/L) | 2.9 | 4.5 | 0.001 | Mild elevation but not critical |
Electrolytea | Pre-HIPEC Average | Post-HIPEC Average | p Value | Clinically Significant |
---|---|---|---|---|
Sodium (mmol/L) | 138.1 | 137.4 | 0.081 | Mild decrease, still within range |
Potassium (mmol/L) | 3.4 | 3.3 | 0.782 | Borderline hypokalemia |
Bicarbonate (mmol/L) | 20.9 | 20.1 | 0.009 | Borderline low |
Glucose (mmol/L) | 201 | 235.5 | 0.001 | Marked hyperglycemia |
Lactate (mmol/L) | 2.5 | 3.4 | <0.001 | Moderately elevated |
Electrolytea | Pre-HIPEC Average | Post-HIPEC Average | p Value | Clinically Significant |
---|---|---|---|---|
Sodium (mmol/L) | 136.4 | 132.7 | 0.001 | Mild hyponatremia in several patients |
Potassium (mmol/L) | 3.7 | 3.3 | 0.001 | Borderline hypokalemia |
Bicarbonate (mmol/L) | 21.8 | 19.6 | 0.001 | Mild metabolic acidosis in some cases |
Glucose (mmol/L) | 180.1 | 299.1 | <0.001 | Marked hyperglycemia |
Lactate (mmol/L) | 2.4 | 7.6 | <0.001 | Lactate > 4 mmol/L in multiple patients |
Parameters | Δ Mean | SD | 95% Confidence Interval | Overall Significance (Kruskal–Wallis) | Significant Pairwise Group Differences (Bonferroni) | p-Value |
---|---|---|---|---|---|---|
Δ Sodium | −1.62 | 4.16 | −2.52 to −0.72 | Yes | Group 2 vs. Group 3 | 0.043 |
Group 2 vs. Group 1 | 0.006 | |||||
Δ Potassium | 0.16 | 0.58 | 0.03 to 0.29 | Yes | Group 2 vs. Group 1 | 0.012 |
Group 2 vs. Group 3 | 0.054 | |||||
Δ Bicarbonate | 1.35 | 2.69 | 0.77 to 1.93 | No | — | 0.099 |
Δ Glucose | 59.73 | 107.52 | 36.46 to 83 | Yes | Group 2 vs. Group 1 | 0.015 |
Group 2 vs. Group 3 | 0.047 | |||||
Δ Lactate | 2.56 | 5.78 | 1.31 to 3.81 | Yes | Group 3 vs. Group 2 | <0.001 |
Groups | Clavien–Dindo 3–4 Morbiditiy (n, %) | 90-Day Mortality (n, %) |
---|---|---|
Mitomycin C + peritoneal dialysate (n = 19) | 4 (21.1%) | 0 (0%) |
Oxaliplatin + D5W (n = 29) | 10 (34.5%) | 0 (0%) |
Oxaliplatin + peritoneal dialysate (n = 34) | 6 (17.6%) | 1 (100%) |
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Argın, V.; Özduman, M.Ö.; Sunar, A.O.; Dinçer, M.; Senger, A.S.; Gülmez, S.; Uzun, O.; Duman, M.; Polat, E. The Effect of Different Intraperitoneal Hyperthermic Chemotherapy (HIPEC) Regimens on Serum Electrolyte Levels: A Comparison of Oxaliplatin and Mitomycin C. Medicina 2025, 61, 1345. https://doi.org/10.3390/medicina61081345
Argın V, Özduman MÖ, Sunar AO, Dinçer M, Senger AS, Gülmez S, Uzun O, Duman M, Polat E. The Effect of Different Intraperitoneal Hyperthermic Chemotherapy (HIPEC) Regimens on Serum Electrolyte Levels: A Comparison of Oxaliplatin and Mitomycin C. Medicina. 2025; 61(8):1345. https://doi.org/10.3390/medicina61081345
Chicago/Turabian StyleArgın, Vural, Mehmet Ömer Özduman, Ahmet Orhan Sunar, Mürşit Dinçer, Aziz Serkan Senger, Selçuk Gülmez, Orhan Uzun, Mustafa Duman, and Erdal Polat. 2025. "The Effect of Different Intraperitoneal Hyperthermic Chemotherapy (HIPEC) Regimens on Serum Electrolyte Levels: A Comparison of Oxaliplatin and Mitomycin C" Medicina 61, no. 8: 1345. https://doi.org/10.3390/medicina61081345
APA StyleArgın, V., Özduman, M. Ö., Sunar, A. O., Dinçer, M., Senger, A. S., Gülmez, S., Uzun, O., Duman, M., & Polat, E. (2025). The Effect of Different Intraperitoneal Hyperthermic Chemotherapy (HIPEC) Regimens on Serum Electrolyte Levels: A Comparison of Oxaliplatin and Mitomycin C. Medicina, 61(8), 1345. https://doi.org/10.3390/medicina61081345